Gangliosides have been implicated in regulation of cell growth and recognition. An unusual synthesis of a unique cell surface fucoganglioside has been found to be induced during an early stage of hepatocarcinogenesis in rats fed the chemical carcinogen N-2-acetylaminofluorene. Once induced, the fucoganglioside is persistently present throughout hepatoma formation and has been determined to be due to induction of a highly specific fucosyltransferase detectable only in premalignant live and hepatoma. These changes may represent specific markers for premalignant and hepatoma cells and may in some way function in the change in cell growth regulation during carcinogenesis. This application proposes to study in detail the process of this change and relate it to premalignant cell markers. The fucosyltransferase will be purified to homogeneity and characterized. Antibodies will be prepared against the fucosyltransferase and fucoganglioside. Cell subpopulations from premalignant livers expressing fucosyltransferase activity will be identified by cellular fractionation and assay of activity and by immunofluorescence staining of cells and tissues by fluorescent antibody directed against the fucosyltransferase and fucoganglioside. Using enzyme assays of cell suspensions and immunofluorescence procedures on liver tissue, the appearance of these antigens during the process of initiation/promotion and complete carcinogenesis will be studied. These cell surface antigens will also be utilized as targets for antibody-toxin conjugates in order to eliminate antigen expressing cells and determine the effect on carcinogenesis. The proposed experiments will determine the nature of the alteration of cell surface gangliosides in terms of specific premalignant cell markers and provide a more rigorous biochemical analysis of their occurrance and function than has been previously demonstrated for current enzyme markers of carcinogenesis in rat liver.